The overall aim of this proposal is to determine whether the endothelial cells of diabetic patients consume less oxygen than in normal cases. To achieve this goal, a novel technique, namely "electron paramagnetic resonance (EPR) oximetry" will be used. EPR oximetry has been developed and successfully utilized in many biological conditions to understand the regulation of respiration in isolated cells. A higher concentration of glucose, known as hyperglycemia, impairs the association of a scaffold protein, heat shock protein 90 (Hsp90) with endothelial nitric oxide syntheses (eNOS). This results in a reduced generation of nitric oxide (NO) and an increased generation of superoxide (O2-). On the other hand, both NO and O2- are known to regulate respiration in the endothelium and hence, excess glucose is expected to alter the respiration of endothelial cells. The aims of this proposal are to measure the respiration at hyperglycemic conditions, as well as hyperglycemic conditions when Hsp90 is over expressed in endothelial cells. The expected outcome of this study is to be able to determine whether hyperglycemic dysfunction of the diabetic endothelium is contributed by an alteration in the respiration. [unreadable] [unreadable] [unreadable]